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A Pilot Study Investigating the Efficacy of Minocycline and N-Acetyl Cysteine for Bipolar Depression

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02719392
Recruitment Status : Recruiting
First Posted : March 25, 2016
Last Update Posted : March 28, 2019
Sponsor:
Information provided by (Responsible Party):
Andrew A. Nierenberg, MD, Massachusetts General Hospital

Brief Summary:
The purpose of the Pilot Study Investigating the Efficacy of Minocycline and n-acetylcysteine for Bipolar Depression is to test the effectiveness of minocycline, n-acetylcysteine, and combined minocycline and n-acetylcysteine pharmacotherapy in order to fill the gap in treatments for bipolar depression. The treatment of bipolar depression remains the greatest unmet need in the management of this lifelong and chronic psychiatric disorder.

Condition or disease Intervention/treatment Phase
Bipolar Disorder Bipolar Depression Dietary Supplement: N-acetylcysteine Drug: Minocycline Other: Placebo Phase 4

Detailed Description:

The investigators are doing this research study to find out if minocycline alone, N-acetyl cysteine (NAC) alone, or the combination of minocycline and NAC can help people with bipolar depression when added to lithium. The investigators also want to find out if minocycline, NAC, and the combination of minocycline and NAC are safe to take without causing too many side effects.

While the U.S. Food and Drug Administration (FDA) has approved minocycline to treat infections and acne and has approved NAC as a mucolytic, the FDA has not approved minocycline, n-acetylcysteine, or the combination of minocycline and n-acetylcysteine to treat bipolar depression.

This research study will compare minocycline, n-acetylcysteine, and the combination of n-acetylcysteine and minocycline to placebo. The placebo looks exactly like the other study drugs, but contains neither minocycline nor NAC. During this study participants may get a placebo instead of minocycline, n-acetylcysteine, or the combination of minocycline and n-acetylcysteine. Placebos are used in research studies to see if the results are due to the study drug or due to other reasons.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Pilot Study Investigating the Efficacy of Minocycline and N-Acetyl Cysteine for Bipolar Depression
Actual Study Start Date : August 9, 2017
Estimated Primary Completion Date : April 2020
Estimated Study Completion Date : June 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Minocycline
Patients in the minocycline group will take 1 minocycline (100mg) and 2 NAC placebo capsules in the morning and 1 minocycline (100mg) and 2 NAC placebo capsules in the evening for a total of 6 capsules per day over the course of the study.
Drug: Minocycline
Minocycline is an FDA-approved antibiotic commonly used to treat bacterial infections.

Other: Placebo
The placebo control is an inactive sugar pill that mimics the active comparators in appearance.

Active Comparator: N-acetylcysteine
Patients in the NAC group will take 2 NAC (500mg) capsules and 1 minocycline placebo capsule in the morning and 2 NAC (500mg) capsules and 1 minocycline placebo capsule in the evening for a total of 6 capsules per day over the course of the study.
Dietary Supplement: N-acetylcysteine
NAC is an FDA-approved mucolytic (a type of drug used to relieve respiratory difficulties) and is also used for the treatment of acetaminophen toxicity.

Other: Placebo
The placebo control is an inactive sugar pill that mimics the active comparators in appearance.

Active Comparator: Minocycline + N-acetylcysteine
Patients in the minocycline NAC combination group will take 2 NAC (500mg) and 1 minocycline (100mg) capsule in the morning and 2 NAC (500mg) and 1 minocycline (100mg) capsule in the evening for a total of 6 capsules per day over the course of the study.
Dietary Supplement: N-acetylcysteine
NAC is an FDA-approved mucolytic (a type of drug used to relieve respiratory difficulties) and is also used for the treatment of acetaminophen toxicity.

Drug: Minocycline
Minocycline is an FDA-approved antibiotic commonly used to treat bacterial infections.

Placebo Comparator: Placebo Control
Patients in the placebo control group will take 2 NAC placebo capsules and 1 minocycline placebo capsule in the morning and 2 NAC placebo capsules and 1 minocycline placebo capsule in the evening for a total of 6 capsules per day over the course of the study.
Other: Placebo
The placebo control is an inactive sugar pill that mimics the active comparators in appearance.




Primary Outcome Measures :
  1. Illness severity on the Clinical Global Impression Scale-Bipolar Version (CGI-BP) [ Time Frame: 8 weeks ]
    The CGI-BP is a modified version of the CGI designed specifically for use in assessing global illness severity and change in patients with bipolar disorder. We will use the overall severity subscale to determine outcome.


Secondary Outcome Measures :
  1. Quality of life on the Quality of Life, Enjoyment, and Satisfaction Questionnaire (QLES-Q) [ Time Frame: 8 weeks ]
    Assesses subjective quality of life (i.e. physical health, subjective feelings, leisure activities and social relationships).

  2. Life satisfaction on the Longitudinal Interval Follow-up Evaluation - Range of Impaired Functioning Tool (LIFE-RIFT) [ Time Frame: 8 weeks ]
    Assesses extent to which psychopathology has impacted current functioning in work, household chores, interpersonal relationships with partner, family, and friends, recreational activities, and life satisfaction.

  3. Depression severity on the Montgomery-Asberg Depression Rating Scale (MADRS) [ Time Frame: 8 weeks ]
    Assesses the severity of depressive symptoms

  4. Mania severity on the Young Mania Rating Scale (YMRS) [ Time Frame: 8 weeks ]
    Assesses the severity of mania and hypomania symptoms



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Able to give written informed consent and follow study procedures
  2. Age > or = 18 years and < or = 65 years
  3. Meets Diagnostic and Statistical Manual of Mental Disorders V (DSM-V) criteria for Bipolar Disorder Type I, which is the primary focus of treatment
  4. Currently depressed, as defined by a Montgomery-Asberg Depression Rating Scale (MADRS) score of > or = 18 at screen and baseline (randomization)
  5. Participants will remain on baseline mood stabilizer pharmacotherapy with lithium during the study. They will need to have been on lithium with stable therapeutic blood levels for at least two weeks prior to randomization and agree not to change medications during the study.
  6. Women of child bearing potential must agree to use adequate contraception (e.g. oral contraceptives, intrauterine device, double barrier methods), if sexually active. Depo Provera is acceptable if it is started 3 months prior to enrollment. If hormonal contraceptives are used, participants must also agree to use a backup method of birth control. They will also need to understand the risks of lithium and other study treatments to the fetus and infant.

Exclusion Criteria:

  1. Unwilling or unable to comply with study requirements
  2. Patients who are a serious suicide or homicide risk, or currently in crisis such that inpatient hospitalization or other crisis management should take priority
  3. DSM-V diagnosis of Bipolar Disorder not otherwise specified, cyclothymia, schizoaffective bipolar type
  4. Primary anxiety disorders (e.g. Panic disorder, generalized anxiety disorder, post-traumatic stress disorder) or patients where the anxiety disorder is the primary focus of treatment
  5. Any history of obsessive compulsive disorder (OCD) or OCD-spectrum disorders
  6. Clinical or laboratory evidence of hypothyroidism; if maintained on thyroid medication must be euthyroid for at least 1 month before Visit 1
  7. Subjects having failed two or more trials of somatic therapy (i.e. medications for bipolar depression or Food and Drug Administration-approved devices) during the current bipolar depressive episode
  8. Drug/alcohol abuse or dependence active within the past 3 months, or current substance use disorder that requires detoxification
  9. Pregnancy (as determined by urine pregnancy test)
  10. Suspected or known clinically unstable systemic medical disorder including epilepsy, untreated endocrine disease, unstable angina, recent ulcers or significant esophagitis
  11. Conditions which may be negatively affected by minocycline treatment, such as inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease)
  12. History of significant treatment non-adherence or situations where the subject is unlikely to adhere to treatment, in the opinion of the investigator
  13. Current use of minocycline or history of anaphylactic reaction or intolerance to minocycline or any component of the preparation
  14. Current use of greater than 500mg of NAC/day, 200ug of selenium/day or 500 IU of Vitamin E/day
  15. History of anaphylactic reaction or intolerance to NAC or any component of the preparation
  16. A primary clinical diagnosis of a personality disorder, or comorbid diagnosis of antisocial or borderline personality disorder
  17. A history of C. difficile colitis
  18. A history of tetracycline allergy
  19. Liver enzymes above the upper limit of normal

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02719392


Contacts
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Contact: Samantha Walsh, B.S. 617-726-0997 swalsh28@partners.org

Locations
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United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Samantha Walsh, B.S.    617-726-0997    swalsh28@partners.org   
Principal Investigator: Andrew A Nierenberg, M.D.         
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
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Principal Investigator: Andrew A Nierenberg, M.D. Massachusetts General Hospital
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Responsible Party: Andrew A. Nierenberg, MD, Director, Bipolar Clinic and Research Program, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT02719392    
Other Study ID Numbers: 2016P000447
First Posted: March 25, 2016    Key Record Dates
Last Update Posted: March 28, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Depression
Depressive Disorder
Bipolar Disorder
Behavioral Symptoms
Mood Disorders
Mental Disorders
Bipolar and Related Disorders
Acetylcysteine
Minocycline
N-monoacetylcystine
Antiviral Agents
Anti-Infective Agents
Expectorants
Respiratory System Agents
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Antidotes
Anti-Bacterial Agents